СУПРАМОЛЕКУЛЯРНАЯ ХИМИЯ

Препаративные методы. Получение супермолекул и

супрамолекулярных ансамблей

Свойства и метаструктура

Эффект «листа лотоса»

Различные формы одного вещества

Technological characteristics

A. Ogienko, Е. Boldyreva, et al., Pharmaceutical Research (2011)

Crystal facet engineering of semiconductor photocatalysts:

motivations, advances and unique properties

Gang Liu, Jimmy C. Yu, Gao Qing (Max) Luc and Hui-Ming Cheng,

Chem. Commun., 2011,47, 6763-6783

Препаративные методы

• Синтез молекул

• Синтез надмолекулярных комплексов с нековалентными взаимодействиями (ротаксаны, катенаны, комплексы циклодекстринов, каликсаренов, кукурбитурилов краун-эфиров и др.)

• Синтез ассоциатов (например, мицелл)

• Синтез двумерных структур (плёнок, в том числе – нанесённых на подложку)

• Модификация поверхности, формы, размера частиц

• Синтез молекулярных кристаллов

• Синтез гибридных структур

• Биохимический синтез

• Синтез устройств

Препаративные методы • Синтез в растворе

• Синтез в расплаве

• Синтез в газе (метод молекулярных пучков)

• Синтез в мицеллах

• Синтез в нанопористых матрицах

• Синтез в слоистых матрицах

• Синтез на подложках

• Синтез в экстремальных условиях (крио-, сверхкритические растворители, высокие давления)

• Механохимический синтез

• Сборка при помощи атомно-силовой микроскопии

• Кристаллизация (различные методы), получение аморфных образцов (различные методы)

Синтез молекул

The Nobel Prize in Chemistry 1987 The Nobel Prize in Chemistry 1987 was awarded jointly to Donald J. Cram, Jean-Marie Lehn and Charles J. Pedersen "for their development and use of molecules with structure-specific interactions of high selectivity".

Стид Дж. В., Этвуд Дж. Л. «Супрамолекулярная химия». — М.: Академкнига, 2007

Синтез молекул

https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2016/popular.html

Краун-эфиры

Другие соединения

12-crown-4, 15-crown-5, 18-crown-6, dibenzo-18-crown-6, and diaza-18-crown-6

[2.2.2]Cryptand (N[CH2CH2OCH2CH2OCH2CH2]3N; 1,10-diaza-4,7,13,16,21,24-hexaoxabicyclo[8.8.8]hexacosane)

клатрохелат криптофан

Антикрауны

Ртуть-12-краун-4(8) Hg-Cl 2.94 Å

каликсарены

Металл-органические каркасы (MOF)

Темплатный синтез

• Катион металла – организующее начало, шаблон

• Рост селективности, выхода

Селективный кинетический эффект: влияет только на одну реакцию, не влияет на побочные

Темплатный синтез

Катенаны (Catenanes)

Олимпиадан

Топологическая связь

Катенаны (Catenanes)

Олимпиадан

Катенаны (Catenanes)

Ротаксаны (Rotaxanes)

Механохимический синтез

Hsueh, S. Y., Cheng, K. W., Lai, C. C., & Chiu, S. H. (2008). Efficient Solvent‐Free Syntheses of [2]‐and [4] Rotaxanes. Angewandte Chemie International Edition, 47(23), 4436-4439.

Waste not want not: A [2]rotaxane has been generated in 49 % yield through the direct grinding of solid macrocyclic, threadlike, and stoppering components. The same solid-state ball-milling reactions of solids of pseudorotaxanes and stoppers produced both [2]- and [4]rotaxanes in high yield (see picture). The approach relies on solid-state condensations and is convenient and waste-free (water is the only by-product).

Механохимический синтез

Small is beautiful: The [2]pseudorotaxane formed from dipropargylammonium tetrafluoroborate and the crown ether [21]crown-7 on SiO2 was stoppered with 1,2,4,5-tetrazine in a ball-milling process (see X-ray structure). This new and efficient solvent-free reaction led to the isolation in high yield (81 %) of the smallest [2]rotaxane reported to date.

Hsu, C. C., Chen, N. C., Lai, C. C., Liu, Y. H., Peng, S. M., & Chiu, S. H. (2008). Solvent‐Free Synthesis of the Smallest Rotaxane Prepared to Date. Angewandte Chemie International Edition, 47(39), 7475-7478.

Молекулярный мускул

Interwoven structures

A twofold interwoven two-dimensional→two-dimensional (2-D→2-D) cluster–organic network based on the [Cu2I2] cluster and the 4,4′-(diazenediyl)dipyridine ligand: poly[[μ2-4,4′-(diazenediyl)dipyridine]-μ2-iodido-copper(I)] Wenjiang Huang,a Jinfang Zhang,b Jianghua Lib and Chi Zhang, Acta Cryst. C, Volume 69| Part 2| February 2013| Pages 123-126

The crystalline architecture of (I), viewed approximately down the b axis, exhibiting the double inter-penetration of the porphyrin networks

Lipstman et al.

Volume 63 | Part 7 | July 2007 | Pages o371–o373 | 10.1107/S0108270107020975

Interwoven hydrogen-bonded network assembly and supramolecular isomerism of meso-5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin as its dimethylformamide solvate

Manipulation of an existing crystal form unexpectedly results in interwoven packing networks with pseudo-translational symmetry

J. M. Reimer, M. N. Aloise, H. R. Powell and T. M. Schmeing

Volume 72 | Part 10 | October 2016 | Pages 1130–1136 | 10.1107/S2059798316013504

Figure 2. Pseudo-independent packing networks in the F-AΔsub structure. (a) The lattice observed in the published crystal structure of the LgrA F-A construct (Reimer et al., 2016 ...

Reimer et al.

Volume 72 | Part 10 | October 2016 | Pages 1130–1136 | 10.1107/S2059798316013504

Protein-directed self-assembly of a fullerene crystal Kook-Han Kim, Dong-Kyun Ko, Yong-Tae Kim, Nam Hyeong Kim, Jaydeep Paul, Shao-Qing Zhang, Christopher B. Murray, Rudresh Acharya, William F. DeGrado, Yong Ho Kim & Gevorg Grigoryan

http://www.nature.com/ncomms/2016/160426/ncomms11429/full/ncomms11429.html

Циклодекстрины

Порфирины

Фталоцианины

Синтез и применение

• Молекулярное распознавание

• Селективность

• Чувствительность к среде и воздействиям

• Имитация биохимических реакций

• Средства доставки лекарств

• Очистка

• Селективная экстракция

• Устройства

Необходимые условия для молекулярного распознавания

• Пространственная комплементарность

• Комплементарность взаимодествий

• Множественность взаимодействий (большая площадь контакта)

• Сильное суммарное связывания

Синтез мицелл и в мицеллах

Обращенная мицелла

Получение нанотрубок, наночастиц, наносфер

Growth characteristics of silicon nanowires synthesized by vapor–liquid–solid growth in nanoporous alumina templates

The fabrication of Si nanowires has been demonstrated using a combination of template-directed synthesis and vapor–liquid–solid (VLS) growth. The use of nanoporous alumina membranes for VLS growth provides control over nanowire diameter while also enabling the production of single crystal material.

• Wu, X. L., Jiang, L. Y., Cao, F. F., Guo, Y. G., & Wan, L. J. (2009). LiFePO4 nanoparticles embedded in a nanoporous carbon matrix: superior cathode material for electrochemical energy‐storage devices. Advanced materials, 21(25‐26), 2710-2714.

• Murillo-Cremaes, N., López-Periago, A. M., Saurina, J., Roig, A., & Domingo, C. (2010). A clean and effective supercritical carbon dioxide method for the host–guest synthesis and encapsulation of photoactive molecules in nanoporous matrices. Green Chemistry, 12(12), 2196-2204.

Получение многокомпонентных кристаллов (cocrystals)

• Роль комплементарных групп (синтоны)

• Роль стерической комплементарности (оптимизация упаковки)

• Термодинамика (фазовые диаграммы)

• Кинетика (метастабильные фазы, зарождение и рост новой фазы)

The complexity of polymorphic transitions in crystalline L-serine depending on the rate of pressure increase

Fisch M., Lanza A.., Boldyreva E., Macchi P., Casati N., Kinetic Control of High-Pressure Solid-State Phase Transitions: Complex High-Pressure Behavior of L-Serine Revisited, J. Phys. Chem. C, 2015, 119 (32), 18611-18617

The effect of Pressure Increasing Rate on the phase composition

• Fisch M., Lanza A.., Boldyreva E., Macchi P., Casati N., Kinetic Control of High-Pressure Solid-State Phase Transitions: Complex High-Pressure Behavior of L-Serine Revisited, J. Phys. Chem. C, 2015, 119 (32), 18611-18617

Zakharov B.A., Goryainov S.V.,

Boldyreva E.V. Unusual seeding

effect in the liquid-assisted high-

pressure polymorphism of

chlorpropamide,

CrystEngComm, 2016, 18 (29) 5423-

5428

Nucleation, Nuclei growth Nuclei growth

Different effect of “inert” media not related to recrystallization

Zakharov B.A., Seryotkin Y.V., Tumanov N.A., Paliwoda D., Hanfland M.,

Kurnosov A.V., Boldyreva E.V. The role of fluids in high-pressure polymorphism

of drugs: Different behaviour of β-chlorpropamide in different inert gas and

liquid media, RSC Advances, 2016, 6 (95), p. 92629-92637

Crystallization at high pressures

• Crystallization of liquids

• Crystallization of solids from their solutions

• Obtaining new phases, which are metastable at ambient conditions, and their quenching

• Search of equilibrium phases at high pressures

• Studying structure-forming units

• Studying intermolecular interactions

Different polymorphs at low temperature and high pressure

Liquid compound A Liquid compound A

Polymorph A1 Polymorph A2

cooling pressure

Both polymorphs can be thermodynamically stable. Their comparison allows to

understand structure-forming factors and crystallization.

Acetic acid

A low-temperature polymorph (16 C) A high-pressure polymorph (0.2 GPa)

Nahringbauer, I. (1970) Allan, D. R., Clark, S. J., Ibberson, R. M.,

Parsons, S., Pulham, C. R., Sawyer, L.

(1999)

Different polymorphs crystallized at different pressures

Liquid compound A Liquid compound A

Polymorph A1 Polymorph A2

Pressure 1 Pressure 2

Both polymorphs can be thermodynamically stable. Their comparison allows to

understand structure-forming factors and crystallization.

The sequence of accessing P1 and P2 may be also important (kinetic factors)

Selected examples from the work done by A. Katrusiak’s group

Olejniczak, A., Katrusiak, A. (2011) Cryst. Growth Design, 11 (6), 2250-2256 Katrusiak, A., Szafrański, M., Podsiadło, (2011) ChemComm, 47 (7), 2107-

2109 Bujak, M., Katrusiak, A. (2010) CrystEngComm, 12 (4), 1263-1268 Olejniczak, A., Katrusiak, A., Szafrański, M. (2010) Cryst Growth Design, 10

(8), 3537-3546 Olejniczak, A., Katrusiak, A. (2010) CrystEngComm, 12 (9), 2528-2532 Dziubek, K., Podsiadlo, M., Katrusiak, A. (2007) J. Am. Chem. Soc. 129,

12620-12621

Pressure-controlled aggregation in carboxylic acids. A case study on the polymorphism of bromochlorofluoroacetic

acid

• Pressure affects the balance between secondary intermolecular interactions involving halogen and oxygen atoms.

• No phase transition between the catemeric and dimeric CBrClFCOOH polymorphs, despite the over-pressurizing phase α by over 1.3 GPa into the stability region of phase β, demonstrates that the preference for dimeric and catemeric forms of carboxylic acids may be impossible for detection as classical solid-state phase transitions, without completely dissolving or melting these compounds and avoiding their nucleation.

• The smaller volume of the β phase, and hence its high-pressure stability, has been rationalized by more freedom of the 0-D dimers to adjust their positions in the crystal structure, compared to the 1-D catemers.

Gajda, R., Katrusiak, A., Crassous, J. (2009) CrystEngComm, 11 (12), 2668-2676

catemer

dimer

No interconversion in the solid state!

Podsiadło, M., Jakóbek, K., Katrusiak, A.

Density, freezing and molecular aggregation in pyridazine, pyridine and benzene (2010)

CrystEngComm 12 (9), pp. 2561-2567

Molecular aggregation of pyridazine (C4H4N 2) and pyridine (C5H5N) has been compared with that of benzene (C6H6) in its phases I and II.

The interactions governing the molecular arrangement in the series of pyridazine, pyridine and benzene structures, gradually change from C-H⋯N to C-H⋯π hydrogen bonds. High pressure also favours the C-H⋯N interactions over the C-H⋯π bonds in pyridine, but benzene remains more stable than pyridazine and pyridine.

Relative role of various weak intermolecular interactions

The role of the exact P, T variation procedure

Liquid compound A Liquid compound A

Polymorph A1 Polymorph A2

Cooling

P ambient Increasing P

T ambient

Increasing P

T = const (low)

Cooling

P = const (high)

Polymorph A3 Polymorph A4

Polymorph A3 Polymorph A4 ≠

No interconversion in the solid state

The role of the exact P, T variation procedure

Liquid compound A

Polycrystalline polymorph A2

Increasing P

T = const

Oscillating T (cooling / heating)

P = const (high)

Single crystal of polymorph A3

Polymorph A5 ≠

No interconversion in the solid state between A3 and A5

Oscillating P

T = const

Single crystal of polymorph A5

Polymorph A3 Polymorph A2 ≠

Crystallization at high pressures

• Crystallization of solids from their solutions

• Crystallization of liquids

• Obtaining new phases, which are metastable at ambient conditions, and their quenching

• Search of equilibrium phases at high pressures

• Studying structure-forming units

• Studying intermolecular interactions

Crystallization at HP

If several polymorphs are known at ambient conditions, the denser one might be the thermodynamically stable form at high pressure, and thus can be crystallized easily and reproduceably at high pressures.

Examples:

• Neumann, M.A., Van De Streek, J., Fabbiani, F.P.A., Hidber, P., Grassmann, O. Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening, Nature Commun, 2015, 6, art. no. 7793

• Polymorph II could be obtained from polymorph I on

direct compressing a powder sample, under a special

compression-decompression procedure, at about 1.9

GPa ; transformation was never complete.

Boldyreva et al, 1999

• Polymorph II could be crystallized from ethanol

solution at 1.1 GPa as single crystals

Fabbiani et al, 2004

• Polymorph II was shown to be the

thermodynamically stable form at high pressures

Ceolin et al, 2005; 2007

Crystallization of solids from their solutions

New solvates of paracetamol

2005-2006

Crystallization of paracetamol II at HP

Crystallization of antibiotics

Fabbiani, F.P.A., Dittrich, B., Florence, A.J., Gelbrich, T., Hursthouse, M.B., Kuhs,

W.F., Shankland, N., Sowa, H. (2009) CrystEngComm, 11 (7), pp. 1396-1406.

Two new ciprofloxacin sodium salts could be obtained at high P and quenched;

A ciprofloxacin hexahydrate grows from the same solution at ambient P

Other examples when solvates are formed at high pressure

• Paracetamol – Fabbiani, F.P.A., Allan, D.R., Dawson, A., David, W.I.F., McGregor, P.A.,

Oswald, I.D.H., Parsons, S., Pulham, C.R. (2003) Chemical Communications, 9 (24), pp. 3004-3005

• Gabapentin heptahydrate – Fabbiani, F.P.A., Levendis, D.C., Buth, G., Kuhs, W.F., Shankland, N., Sowa, H.

(2010) CrystEngComm, 12 (8), pp. 2354-2360

• 1,4-diazabicyclo[2.2.2]octane hydroiodide (dabcoHI) hydrate – Olejniczak, A., Katrusiak, A. (2011) Cryst. Growth Design, 11 (6), pp.

2250-2256

Growth of L-alanine solvates

N. Tumanov, E. Boldyreva, et al., Acta Cryst. 2010, vol. B66, p. 458-471

Inclusion of alkanes into MOFs

Pressures up to 0.8 GPa have been used to squeeze a range of

sterically “oversized” C5–C8 alkane guest molecules into the cavities of

a small-pore Sc-based metal–organic framework.

McKellar, S.C., Sotelo, J., Greenaway, A., Mowat, J.P.S., Kvam, O.,

Morrison, C.A., Wright, P.A., Moggach, S.A. (2016) Chemistry of

Materials, 28 (2), pp. 466-473.

72

Ogienko, A. G., Bogdanova, E. G., Trofimov, N. A., Myz, S. A., Ogienko, A. A., Kolesov, B. A., ... & Boldyreva, E. V. (2017). Large porous particles for respiratory drug delivery. Glycine-based formulations. European Journal of Pharmaceutical Sciences.

AFM and supramolecular assembling

A strategy for the chemical synthesis of nanostructures Muller, Wolfgang T; Klein, David L; Lee, Thomas; Clarke, John; et al. Science; Washington268.5208 (Apr 14, 1995): 272.

Препаративные методы

• Синтез молекул

• Синтез надмолекулярных комплексов с нековалентными взаимодействиями (ротаксаны, катенаны, комплексы циклодекстринов, каликсаренов, кукурбитурилов краун-эфиров и др.)

• Синтез ассоциатов (например, мицелл)

• Синтез двумерных структур (плёнок, в том числе – нанесённых на подложку)

• Модификация поверхности, формы, размера частиц

• Синтез молекулярных кристаллов

• Синтез гибридных структур

• Биохимический синтез

• Синтез устройств

Препаративные методы • Синтез в растворе

• Синтез в расплаве

• Синтез в газе (метод молекулярных пучков)

• Синтез в мицеллах

• Синтез в нанопористых матрицах

• Синтез в слоистых матрицах

• Синтез на подложках

• Синтез в экстремальных условиях (крио-, сверхкритические растворители, высокие давления)

• Механохимический синтез

• Сборка при помощи атомно-силовой микроскопии

• Кристаллизация (различные методы), получение аморфных образцов (различные методы)